Field of the Invention
The present invention relates to methods and apparatuses for increasing the efficacy of therapeutic compounds delivered to tissues affected by disease, and more specifically, to methods and apparatuses for increasing the efficacy of therapeutic compounds delivered to targeted tissue, especially brain tissue, using ultrasound.
Background of the Invention
A large number of Americans each year suffer from diseases affecting the brain such as cancer, Alzheimer's, Parkinson's Syndrome, and other illnesses. However, the efficacy of such treatments is significantly reduced as a result of the blood-brain barrier which serves as a boundary between blood and fluid from the central nervous system. The blood-brain barrier significantly reduces the ability of therapeutic compounds placed within the bloodstream to cross this boundary and effectively act upon targeted tissue. This is especially true for therapeutic compounds consisting of larger molecules. As a result, the blood-brain barrier significantly reduces the ability of therapeutic compounds delivered into the bloodstream to reach targeted tissue across the barrier thereby significantly reducing the possibility of effective treatment of the disease. As such, there is an interest in developing of targeted therapeutic compound delivery systems which can enhance the ability of these compounds to cross the blood-brain barrier.
In order to treat such diseases, some current methods deliver therapeutic compounds directly to areas of the brain affected by the disease to bypass any complications arising as a result of the blood-brain barrier. It is particularly important, especially in sensitive areas such as the brain, to increase efficacy of such compounds placed in the bloodstream by more directly targeting the affected tissue with the delivered drugs. This can reduce the need for higher concentrations of the compounds and reduce the amount any adverse effects on neighboring healthy tissue.
Current methods and devices use various fluid infusion techniques under pressure, sometimes termed convection-enhanced delivery (CED), to conduct targeted therapeutic compound delivery to targeted brain tissue. These methods involve connecting a pump to a catheter to drive fluid containing a therapeutic compound into the targeted tissue. However, since these techniques require volumetric infusion into a closed vessel (i.e., the cranium), pressures within the closed vessel increase. In highly sensitive areas, such as the brain, there is a limit to the amount of pressure increase, and therefore the amount of infusion possible, before injuries are sustained as a result of stresses and strains caused by the increased pressures. As such, limits are placed on the amount of enhancement that can be achieved using current CED techniques. Additionally, current CED techniques have been shown to oftentimes not reach the targeted location. Furthermore, other complications arise which further reduce the efficacy of this treatment method such as fluid traveling back along the catheter and away from the targeted area (i.e., backflow).
As such, while CED therapies have shown promise, there is a general desire to continue to improve the methods and apparatuses involved with such therapy.